The proposed studies will focus on the ability of drugs which have been found to increase or decrease the severity of human depression to produce analogous behavioral effects in a nonhuman primate model of depression. The main objective is to determine which classes of psychoactive drugs exacerbate or alleviate the despair response to social separation in rhesus monkeys. Several different classes of drugs will be examined in order to determine whether despair behavior in monkeys has a drug interaction profile which is similar to that established for human depression. The technique of repeated peer separation with concurrent drug treatment will be utilized to evaluate the degree to which pharmacological treatments may interact with separation from attachment objects and either exacerbate or ameliorate the despair response. Assay of cerebrospinal fluid and urinary biogenic amine metabolites will provide a correlative measure of the nature and magnitude of drug effects which may be associated with altered behavior patterns. The behavioral and biochemical effects of long-term alteration of brain catecholamine metabolism following intracerebral injection of 6-hydroxydopamine will also be examined within the peer separation paradigm. These investigations will provide an indication of the nature and magnitude of alterations in brain biogenic amine metabolism which may significantly alter the response of individuals to events such as social separation. Concurrent studies of biogenic amine metabolites obtainable from body fluids will allow a determination of the probability of detecting changes in these measures which have important behavioral correlates in a primate population.